The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies

Pharmacol Ther. 2007 Jan;113(1):1-15. doi: 10.1016/j.pharmthera.2006.06.008. Epub 2006 Aug 4.


Histamine neurons are exclusively located in the posterior hypothalamus, and project their fibers to almost all regions of the human brain. Although a significant amount of research has been done to clarify the functions of the histaminergic neuron system in animals, a few studies have been reported on the roles of this system in the human brain. In past studies, we have been able to clarify some of the functions of histamine neurons using different methods, such as histamine-related gene knockout mice or human positron emission tomography (PET). The histaminergic neuron system is known to modulate wakefulness, the sleep-wake cycle, appetite control, learning, memory and emotion. Accordingly we have proposed that histamine neurons have a dual effect on the CNS, with both stimulatory and suppressive actions. As a stimulator, neuronal histamine is one of the most important systems that stimulate and maintain wakefulness. Brain histamine also functions as a suppressor in bioprotection against various noxious and unfavorable stimuli of convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress susceptibility. This review summarizes our works on the functions of histamine neurons using human PET studies, including the development of radiolabeled tracers for histamine H1 receptors (H1R: (11)C-doxepin and (11)C-pyrilamine), PET measurements of H1R in depression, schizophrenia, and Alzheimer's disease (AD), and studies on the sedative effects of antihistamines using H(2)(15)O and H1R occupancy in the human brain. These molecular and functional PET studies in humans are useful for drug development in this millennium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Animals
  • Binding, Competitive
  • Histamine / metabolism*
  • Histamine H1 Antagonists / metabolism
  • Histamine H1 Antagonists / pharmacology
  • Histamine H1 Antagonists, Non-Sedating / metabolism
  • Histamine H1 Antagonists, Non-Sedating / pharmacology
  • Humans
  • Hypothalamus / diagnostic imaging
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Mental Disorders / diagnostic imaging
  • Mental Disorders / metabolism
  • Mental Disorders / physiopathology*
  • Nervous System Diseases / diagnostic imaging
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / physiopathology*
  • Neurons / diagnostic imaging
  • Neurons / drug effects
  • Neurons / metabolism*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / metabolism
  • Receptors, Histamine / drug effects
  • Receptors, Histamine / metabolism*
  • Sleep / drug effects
  • Wakefulness / drug effects


  • Histamine H1 Antagonists
  • Histamine H1 Antagonists, Non-Sedating
  • Radiopharmaceuticals
  • Receptors, Histamine
  • Histamine